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Gli1 Is an Inducing Factor in Generating Floor Plate Progenitor Cells from Human Embryonic Stem Cells

Denham, Mark LU ; Thompson, Lachlan LU ; Leung, Jessie; Pebay, Alice; Björklund, Anders LU and Dottori, Mirella (2010) In Stem Cells 28(10). p.1805-1815
Abstract
Generation of mesencephalic dopamine (mesDA) neurons from human embryonic stem cells (hESCs) requires several stages of signaling from various extrinsic and intrinsic factors. To date, most methods incorporate exogenous treatment of Sonic hedgehog (SHH) to derive mesDA neurons. However, we and others have shown that this approach is inefficient for generating FOXA2+ cells, the precursors of mesDA neurons. As mesDA neurons are derived from the ventral floor plate (FP) regions of the embryonic neural tube, we sought to develop a system to derive FP cells from hESC. We show that forced expression of the transcription factor GLI1 in hESC at the earliest stage of neural induction, resulted in their commitment to FP lineage. The GLI1+ cells... (More)
Generation of mesencephalic dopamine (mesDA) neurons from human embryonic stem cells (hESCs) requires several stages of signaling from various extrinsic and intrinsic factors. To date, most methods incorporate exogenous treatment of Sonic hedgehog (SHH) to derive mesDA neurons. However, we and others have shown that this approach is inefficient for generating FOXA2+ cells, the precursors of mesDA neurons. As mesDA neurons are derived from the ventral floor plate (FP) regions of the embryonic neural tube, we sought to develop a system to derive FP cells from hESC. We show that forced expression of the transcription factor GLI1 in hESC at the earliest stage of neural induction, resulted in their commitment to FP lineage. The GLI1+ cells coexpressed FP markers, FOXA2 and Corin, and displayed exocrine SHH activity by ventrally patterning the surrounding neural progenitors. This system results in 63% FOXA2+ cells at the neural progenitor stage of hESC differentiation. The GLI1-transduced cells were also able to differentiate to neurons expressing tyrosine hydroxylase. This study demonstrates that GLI1 is a determinant of FP specification in hESC and describes a highly robust and efficient in vitro model system that mimics the ventral neural tube organizer. STEM CELLS 2010; 28: 1805-1815 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Dopamine neuron, Parkinson's disease, GLI1, Human embryonic stem cell
in
Stem Cells
volume
28
issue
10
pages
1805 - 1815
publisher
AlphaMed Press
external identifiers
  • wos:000284104100010
  • scopus:78149300886
ISSN
1549-4918
DOI
10.1002/stem.510
language
English
LU publication?
yes
id
cd34edf1-aef4-4da9-a2ab-6fa384818810 (old id 1752734)
date added to LUP
2011-01-04 07:38:46
date last changed
2018-06-10 04:14:20
@article{cd34edf1-aef4-4da9-a2ab-6fa384818810,
  abstract     = {Generation of mesencephalic dopamine (mesDA) neurons from human embryonic stem cells (hESCs) requires several stages of signaling from various extrinsic and intrinsic factors. To date, most methods incorporate exogenous treatment of Sonic hedgehog (SHH) to derive mesDA neurons. However, we and others have shown that this approach is inefficient for generating FOXA2+ cells, the precursors of mesDA neurons. As mesDA neurons are derived from the ventral floor plate (FP) regions of the embryonic neural tube, we sought to develop a system to derive FP cells from hESC. We show that forced expression of the transcription factor GLI1 in hESC at the earliest stage of neural induction, resulted in their commitment to FP lineage. The GLI1+ cells coexpressed FP markers, FOXA2 and Corin, and displayed exocrine SHH activity by ventrally patterning the surrounding neural progenitors. This system results in 63% FOXA2+ cells at the neural progenitor stage of hESC differentiation. The GLI1-transduced cells were also able to differentiate to neurons expressing tyrosine hydroxylase. This study demonstrates that GLI1 is a determinant of FP specification in hESC and describes a highly robust and efficient in vitro model system that mimics the ventral neural tube organizer. STEM CELLS 2010; 28: 1805-1815},
  author       = {Denham, Mark and Thompson, Lachlan and Leung, Jessie and Pebay, Alice and Björklund, Anders and Dottori, Mirella},
  issn         = {1549-4918},
  keyword      = {Dopamine neuron,Parkinson's disease,GLI1,Human embryonic stem cell},
  language     = {eng},
  number       = {10},
  pages        = {1805--1815},
  publisher    = {AlphaMed Press},
  series       = {Stem Cells},
  title        = {Gli1 Is an Inducing Factor in Generating Floor Plate Progenitor Cells from Human Embryonic Stem Cells},
  url          = {http://dx.doi.org/10.1002/stem.510},
  volume       = {28},
  year         = {2010},
}